Horizon Therapeutics announces Krystexxa, pipeline updates
Horizon Therapeutics announced that it is increasing the peak U.S. annual net sales expectations for its key growth drivers Krystexxa and teprotumumab, as well as providing several pipeline updates. Based on current strong performance, the company is increasing its peak U.S. annual net sales expectation for Krystexxa to more than $1B, from the previous expectation of more than $750M. The company continues to project Krystexxa FY19 net sales growth of more than 25%. The company also announced topline results from its MIRROR open-label pilot study, which evaluated the use of the immunomodulator methotrexate with Krystexxa to increase the response rate of Krystexxa. The results of the study demonstrated that 79%, or 11 of 14 patients, achieved a complete response, defined as the proportion of serum uric acid, or sUA, responders at Month 6. The combination was also well tolerated. Detailed results from the study will be presented at a future medical meeting. The 79% response rate is significantly higher than the 42% response rate in the Krystexxa Phase 3 clinical program, which evaluated Krystexxa alone. Krystexxa has demonstrated rapid reduction in sUA levels for people with uncontrolled gout; however, treatment with biologic medicines can, in some patients, trigger the body's immune system to develop anti-drug antibodies. These anti-drug antibodies can reduce the effectiveness of the biologic therapy. Immunomodulators such as methotrexate, which is commonly used by rheumatologists, can help reduce this reaction. The MIRROR open-label pilot study follows other studies that showed an improved response rate when Krystexxa is co-administered with methotrexate. There is a growing body of data supporting the potential of Krystexxa plus immunomodulation to become the standard therapy opposed to Krystexxa therapy alone. The company is currently conducting a separate, placebo-controlled MIRROR trial evaluating the use of Krystexxa and methotrexate. The trial, with 135 randomized patients, is designed to enable the potential for submission of results to the FDA for update to the label. In addition, the company is planning to evaluate the impact of administering Krystexxa over a significantly shorter infusion duration. The initial proof-of-concept work will begin mid-2020. Currently, Krystexxa is infused over a two-hour or longer timeframe. A shorter infusion duration could meaningfully improve the experience and convenience for patients, physicians and sites of care. Additionally, the company is evaluating additional indications for teprotumumab and is initiating an exploratory study in diffuse cutaneous scleroderma, a rare fibrotic disease with no treatment options. Diffuse cutaneous scleroderma is a subtype of scleroderma in which excess collagen production causes skin thickening and hardening, or fibrosis, over large areas of the body, usually the fingers, hands, arms, anterior trunk, legs and face. There can be significant associated organ damage, including to the gastrointestinal tract, kidneys, lungs and heart. Literature suggests that the mechanism of action of teprotumumab, which is to block the IGF-1 receptor, could have an impact on fibrotic processes, such as those that are relevant to diffuse cutaneous scleroderma. The company expects to conduct an exploratory trial beginning in the first half of 2020 to evaluate objective biomarker and clinical endpoints to inform potential subsequent larger and longer duration clinical trials.